The physiological function and the mode of regulation of the transglutaminases are being studied including their role in the modulation of specific cellular processes and in fibrin-connective tissue matrix stabilization during tissue repair. A novel form of transglutaminase, distributed in cell membranes and nuclei, has been isolated and characterized. This membrane-associated transglutaminase, which is present as an inactive form in resting cells, is one of the first enzymes to be activated during cell stimulation and proliferation. The physiological significance and biochemical mechanism of Factor XIIIa (plasma transglutaminase)-catalyzed crosslinking of fast-reacting plasmin inhibitor (Alpha 2-PI) to fibrin and other matrix proteins is under investigation both in vivo (Shwartzman's phenomenon) and in vitro. Fibrin crosslinked to Alpha 2-PI has been shown to be resistant to plasminolysis.